Late Effects of 1H + 16O on Short-Term and Object Memory, Hippocampal Dendritic Morphology and Mutagenesis

Frederico Kiffer; Tyler Alexander; Julie Anderson; Thomas Groves; Taylor McElroy; Jing Wang; Vijayalakshmi Sridharan; Michael Bauer; Marjan Boerma; Antiño Allen

doi:10.3389/fnbeh.2020.00096

Late Effects of ¹H + ¹⁶O on Short-Term and Object Memory, Hippocampal Dendritic Morphology and Mutagenesis

Front Behav Neurosci. 2020 Jun 26:14:96. doi: 10.3389/fnbeh.2020.00096. eCollection 2020.

Authors

Frederico Kiffer^{1

2}, Tyler Alexander^{1

2}, Julie Anderson^{1

2}, Thomas Groves^{1

2

3}, Taylor McElroy^{1

2}, Jing Wang^{1

2}, Vijayalakshmi Sridharan^{1

2}, Michael Bauer⁴, Marjan Boerma^{1

2}, Antiño Allen^{1

2

3}

Affiliations

¹ Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
² Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
³ Neurobiology & Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
⁴ Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, AR, United States.

Abstract

The space extending beyond Earth's magnetosphere is subject to a complex field of high-energy charged nuclei, which are capable of traversing spacecraft shielding and human tissues, inducing dense ionization events. The central nervous system is a major area of concern for astronauts who will be exposed to the deep-space radiation environment on a mission to Mars, as charged-particle radiation has been shown to elicit changes to the dendritic arbor within the hippocampus of rodents, and related cognitive-behavioral deficits. We exposed 6-month-old male mice to whole-body ¹H (0.5 Gy; 150 MeV/n; 18-19 cGy/minute) and an hour later to ¹⁶O (0.1Gy; 600 MeV/n; 18-33 Gy/min) at NASA's Space Radiation Laboratory as a galactic cosmic ray-relevant model. Animals were housed with bedding which provides cognitive enrichment. Mice were tested for cognitive behavior 9 months after exposure to elucidate late radiation effects. Radiation induced significant deficits in novel object recognition and short-term spatial memory (Y-maze). Additionally, we observed opposing morphological differences between the mature granular and pyramidal neurons throughout the hippocampus, with increased dendritic length in the dorsal dentate gyrus and reduced length and complexity in the CA1 subregion of the hippocampus. Dendritic spine analyses revealed a severe reduction in mushroom spine density throughout the hippocampus of irradiated animals. Finally, we detected no general effect of radiation on single-nucleotide polymorphisms in immediate early genes, and genes involved in inflammation but found a higher variant allele frequency in the antioxidants thioredoxin reductase 2 and 3 loci.

Keywords: Mars; behavior; brain; hippocampus; morphology; neuron; radiation; space.

Abstract

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